Patent IL-38964-A (IL)
Title: 16,17-byclopropa androstanes,their preparation and pharmaceutical compositions containing them
IPC: C07J1/00
Filed: 1972-03-13
Abstract: 1367384 16,17-Cyclopropano steroids F HOFFMANN-LA ROCHE & CO AG 14 March 1972 [15 March 1971] 11778/72 Heading C2U The invention comprises compounds of formula wherein X 1 and X 2 are each H or F; R 17 is H, C 1-8 alkyl, C 3-8 cycloalkyl or C 1-8 acyl; R 2 is H; R 3 is 3-oxo optionally with #<SP>1</SP>, #<SP>4</SP>, #<SP>1,4</SP>, #<SP>4,6</SP> or #<SP>1,4,6</SP> unsaturation, or 3-OR optionally with #<SP>5</SP> unsaturation (R being H, C 1-20 acyl, C 1-8 alkyl, aryl-C 1-8 alkyl or C 3-8 cycloalkyl); or R 2 , R 3 and the 2- and 3-carbon atoms together form a 5- membered heteroaromatic ring in which a heteroatom is attached to the steroid 3-carbon atom, optionally with #<SP>4</SP> or #<SP>4,8</SP> unsaturation; and R 7 is H, or when R 3 is 3-oxo optionally with #<SP>4</SP> or #<SP>1,4</SP> unsaturation, R 7 is H, SH, C 1-20 acylthio or C 1-8 alkylthio. Compounds I (other than 3-oxo and 17- hydroxy compounds) are prepared from the corresponding #<SP>16</SP>-compounds by addition of CX 1 X 2 across the 16-double bond, e.g. by reaction with CH 2 I 2 or CH 2 Br 2 in the presence of Zn-Cu couple or a dialkylzinc, or with a mono- or difluorocarbene which may be formed in situ by pyrolysis of sodium chlorodifluoroacetate in diglyme. Other compounds I are prepared from these by one or more steps selected from: (i) oxidation of 3-hydroxy to oxo; (ii) introduction of a 2,3-fused hetero ring via 2-hydroxymethylene intermediates (vide infra); (iii) 3- and/or 17- esterification, etherification, de-esterification or de-etherification; (iv) #<SP>1</SP>, #<SP>4</SP> and/or #<SP>6</SP> dehydrogenation; (v) selective 1,2-hydrogenation; (vi) adding R<SP>1</SP>SH across a #<SP>6</SP> double bond (R<SP>1</SP> being H, alkyl or acyl); or (vii) hydrolysing a 7-acylthio group. In Example 17, a 3-oxo compound I is prepared by hydrolysis of a corresponding 3,3- ethylenedioxy compound. 3#-Benzyloxy - 17 - acetoxy - 5α - androst - 16- ene (XI) is prepared from 3#-hydroxy-17,17- ethylenedioxy-5α-androstane (X) by the sequence : X # 3#-benzyloxy-17,17-ethylenedioxy- 5α - androstane # 3# - benzyloxy- 5α-androstan- 17-one # XI (Exx. 5-7). 3,3 - Ethylenedioxy - 17# - propionyloxy - 16#,- 17-dihydro - 3<SP>1</SP>H - cycloprop[16,17] - 5α - androstane is prepared from the corresponding 3-oxo- 17#-acetoxy compound via the corresponding 3,3-ethylenedioxy - 17# - acetoxy and 3,3 - ethylenedioxy-17#-hydroxy compounds (Exx. 16-17). 3# - Benzoyloxy - 17 - acetoxy - 5α - androst - 16- ene is prepared from epiandrosterone benzoate by reaction with isopropenyl acetate (Ex. 39). 2-Hydroxymethylene-17#-(acetoxy, methoxy, ethoxy and propoxy)-16#,17-dihydro-3<SP>1</SP>H-cycloprop[16,17]-5α-androstan-3-one are prepared from the corresponding 2-unsubstituted compounds by reaction with HCO 2 Et/NaOMe/py (Exx. 28, 34, 44, 47). 3#-Acetoxy-17-(methoxy, ethoxy and propoxy)- 5α-androst-16-ene are prepared from epiandrosterone acetate via 3#-acetoxy-17,17-(dimethoxy, diethoxy and dipropoxy)-5α-androstane (Exx. 24, 25, 32, 41). Anabolic and androgenic compositions for oral and parenteral administration comprise a compound of Formula I and a carrier.
[GB1367384A]